This research proposes a thorough and systematic microrheological study of the flow patterns and distributions of fluid velocity and shear rate in various regions of disturbed flow in the human and dog aortic and cerebral circulation. This will be achieved through direct observation and filming of the behavior of blood cells and model particles flowing in isolated transparent natural vessels prepared from post-mortem humans and dogs by the method recently developed by the applicant. Specific aims of the proposed research are: (1) to obtain precise and detailed flow patterns in regions of disturbed flow in the human and canine circulation under normal (physiological) and altered flow conditions; (2) to acquire information on the distributions of fluid velocity and shear rate existing in the regions of disturbed flow in order to identify the regions of high and low shear; (3) to compare the results with that previously obtained in various model studies in order to find out the specific feature of the geometrical structure and the flow patterns in natural vessels; and (4) to correlate the results with the incidences of vascular diseases in vivo. Long term objectives of the proposed research are: (1) to arrive at a better understanding of fluid dynamics of the mammalian circulation under normal (physiological) and altered flow conditions; and (2) to clarify the possible connection between flow and the localization of thrombosis and atherosclerosis. Significance of the proposed research is that the method has, for the first time, been systematically applied to the study of the fluid mechanics in natural vessels to elucidate the effect of fluid mechanical factors on the genesis and development of thrombosis and atherosclerosis. The knowledge acquired from these investigations will help not only to understand the fluid dynamics of the mammalian circulation but also to design optimal flow channels in artificial organs and prosthetic devices which suffer from the common problem of thrombus formation. Finally such knowledge would provide some insight into the consequences of the altered flow patterns in post-operative thrombosis in vessels that have undergone vascular surgery such as coronary by-pass operations and other procedures involving resection of arteries and veins.